ATO consolidation results in excellent survival in pediatric patients with newly diagnosed APL: A report from the Children’s Oncology Group Study AAML0631

Background

The European acute promyelocytic leukemia (APL) group identified an increased risk of relapse in pediatric patients with APL less than 5 years of age.1 At the 7th International Symposium on APL, survival and relapse outcomes from a cooperative group trial of pediatric patients with newly diagnosed APL were presented.2

Study design

The AAML0631 study was a phase III, nonrandomized, cooperative group trial using arsenic trioxide (ATO) consolidation in pediatric patients with APL.

Data from pediatric patients in the Italian AIDA0493 trial were used as a historical control.3

Eligibility criteria included age ≥2 to <22 years, de novo APL as confirmed by promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARα) translocation by polymerase chain reaction (PCR), and no prior therapy.

There were no exclusions based on organ function or performance score.

For SR patients with no Consolidation 4 treatment, 355 mg/m2 daunorubicin equivalents were used (assuming 5:1 conversion ratio for both idarubicin and mitoxantrone to daunorubicin), resulting in a 45% reduction in anthracycline when compared with the AIDA0493 study.3

For HR and SR patients with positive results in real-time quantitative reverse transcriptase PCR (RQ-PCR; i.e., with Consolidation 4 treatment), 405 mg/m2 daunorubicin equivalents were used, resulting in a 38% reduction in anthracycline when compared with the AIDA0493 study.3

Study design

Key findings

Trial accrual was open between March 9, 2009 and November 9, 2012.

A total of 108 patients were enrolled in the study, with 101 patients (66 SR patients and 35 HR patients) evaluable for treatment outcome.

There were seven exclusions: four that were PML-RARα PCR negative and three that had local consent issues.

In the current analysis, patients were stratified by the following age groups:

Young children (2 to <5 years; n = 6);

Older children (5 to <13 years; n = 27); and

Adolescents (13 to <22 years; n = 68).

Sixty-seven percent of young children, 22% of older children, and 37% of adolescents enrolled were in the HR group (three-way comparison of HR proportion: p = 0.096).

The classic PML-RARα translocation between chromosomes 15 and 17 (t[15;17]) was present in five young children (83%), 11 older children (42%), and 46 adolescents (70%).

Complex cytogenetics (PML-RARα t[15;17] in combination with other cytogenetic abnormalities) were identified in one young child (17%), 15 older children (58%), and 20 adolescents (30%) (three-way comparison of complex cytogenetics: p = 0.028).

The 3-year overall survival rate was 100% for both young and older children, and 91% for adolescents (p = 0.324).

The 3-year event-free survival was 100%, 96%, and 88% for young children, older children, and adolescents, respectively (p = 0.540).

The 3-year risk of relapse (from the end of consolidation) was 0% for young children, 4% for older children, and 3% for adolescents (p = 0.888).

Key Conclusions

Although limited by small numbers, data from this analysis show similar outcomes in all pediatric age groups treated in the study.

This suggests young age should not be used for risk stratification in APL when therapy includes ATO consolidation.